S849 Bone Density and Fracture Risk in Vonoprazan Users: A Stratified Population-Based Analysis

Introduction: Proton pump inhibitors are among the most prescribed medications in the U.S., with an estimated 92 million prescriptions written in 2022 alone. While widely used and readily available over the counter, they have been associated with osteoporosis, which can be life-threatening in cases. With the U.S. Food and Drug Administration approval of vonoprazan in 2023 and its increasing use due to its superior efficacy in treating erosive esophagitis, peptic ulcer disease, and Helicobacter pylori infection, evaluating its potential impact on bone health is crucial. Methods: A retrospective cohort study was conducted using the TriNetX database to determine the risk for developing osteopenia or osteoporosis in vonoprazan users for gastroesophageal reflux disease overall and by age, sex, and race as the primary outcome. Additionally, the risk of fragility fracture was calculated as a secondary outcome. Those with prior history of the primary or secondary outcome, development under 6 months of vonoprazan initiation, metabolic bone disease, or use of confounding drugs within 1 month were excluded. Results: A total of 17,690 vonoprazan users and 2,389,116 non-users were identified. Among those, 1,345 (7.6%) developed osteopenia or osteoporosis 6 months after starting the vonoprazan compared to 187,159 (8.5%) non-users, with a relative risk (RR) of 0.971 (P = 0.255; 0.92-1.02). Risk among men was 0.776 (P < 0.05; 0.68-0.89) and 1.19 (P < 0.05; 1.13-1.26) for women. For those younger than 50, RR 0.53 (P < 0.05; 0.32-0.88]) vs those 50 years or older RR 0.77 (P < 0.05; 0.73-0.81). Among those that developed osteoporosis or osteopenia, fragility fractures occurred in 119 (8.9%) vonoprazan users compared to 9,932 (5.3%) with RR 1.67 (P < 0.05; 1.40-1.98). Conclusion: These findings suggest that vonoprazan does not significantly increase the risk of bone density loss among the general population; subgroup analysis revealed male users had a lower risk, whereas female users had a higher risk. This sex divergence may reflect underlying hormonal differences, as demonstrated by a modest increase in risk in women older than 50 years. Notably, despite the lack of a significant association with reduced bone density overall, vonoprazan users who did develop osteopenia or osteoporosis experienced a substantially higher rate of fragility fractures. This finding is clinically important, as fragility fractures are a direct consequence of compromised bone integrity and are associated with substantial morbidity and mortality, particularly in older adults.